E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Asymptomatic or mildly symptomatic chemotherapy-naïve bone predominant metastatic castration-resistant prostate cancer |
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E.1.1.1 | Medical condition in easily understood language |
patients with prostate cancer with no symptoms or with mild symptoms with metastases mainly in bones, who never had chemotherapy |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036909 |
E.1.2 | Term | Prostate cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to compare the clinical benefit of radium-223 dichloride versus placebo in combination with abiraterone and prednisone/prednisolone in asymptomatic or mildly symptomatic chemotherapynaïve bone predominant metastatic castration-resistant prostate cancer patients. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to compare overal survival, time to opiate use for cancer pain, time to pain progression, time to cytotoxic chemotherapy, radiological progression free survival, acute and long term safety. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Histologically confirmed adenocarcinoma of the prostate - Male subjects of age ≥ 18 yearsThe lower limit may be higher if legally required in the participating country - Prostate cancer progression documented by prostate specific antigen according to the Prostate Cancer Working Group 2 (PCWG2) criteria or radiological progression according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. - Two or more bone metastases on bone scan within 4 weeks prior to randomization with no lung, liver, other visceral and/or brain metastasis. - Asymptomatic or mildly symptomatic prostate cancer. - Subjects who received combined androgen blockade with an anti-androgen must have shown PSA progression after discontinuing the anti-androgen prior to enrollment. - Maintenance of medical castration3 or surgical castration with testosterone less than 50 ng/dL (1.7 nmol/L). If the subject is being treated with luteinizing hormonereleasing hormone (LHRH) agonists or antagonists (subject who has not undergone orchiectomy), this therapy must have been initiated at least 4 weeks prior to randomization and must be continued throughout the study. - Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 |
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E.4 | Principal exclusion criteria |
- Prior cytotoxic chemotherapy for the treatment of CRPC, including taxanes, mitoxantrone and estramustine - Administration of immunotherapies (e.g., sipuleucel-T) within 4 weeks before randomization - Any chronic medical condition requiring a higher dose of corticosteroid than 5 mg prednisone/prednisolone twice daily. - Pathological finding consistent with small cell carcinoma of the prostate - History of visceral metastasis, or presence of visceral metastasis detected by screening imaging examinations - History of or known brain metastasis. - Malignant lymphadenopathy exceeding 3 cm in shortaxis diameter. - Blood transfusion or erythropoietin stimulating agents prior 4 weeks of screening and during the whole screening period before randomization - Imminent spinal cord compression based on clinical findings and/or magnetic resonance imaging (MRI). Subjects with history of spinal cord compression should have completely recovered - Use of opiate analgesics for cancer-related pain, including codeine and dextropropoxyphene, currently or anytime during the 4- week period prior to randomization. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Symptomatic skeletal event free survival(SSE-FS) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Overall Survival 2. Time to opiate use for cancer pain 3. Time to pain progression 4. Time to cytotoxic chemotherapy 5. Radiological progression free survival (rPFS) 6. Number of participants with adverse events as a measure of safety and tolerability |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. At 3 years for interim At 6 years for final 2. At 3 years 3. At 3 years 4. At 3 years 5. At 3 years 6. Up to 3 years Evaluation of efficacy and exploratory endpoints (except OS) will be discontinued following the final OS analysis. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 67 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Brazil |
Canada |
China |
Israel |
Japan |
United States |
Russian Federation |
Belgium |
Finland |
France |
Germany |
Italy |
Netherlands |
Norway |
Poland |
Spain |
Sweden |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study (EOS) is defined as the date of the last subject last visit (LSLV) in the study. The EOS will occur at the time the last subject on study completes 7 years of follow-up unless the subject dies, withdraws consent or is lost to follow-up (FU). |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |